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翻白草通过 Nrf2 通路对离体大鼠心脏缺血/再灌注模型的心脏保护和抗细胞凋亡作用。

Cardioprotective and anti-apoptotic effects of Potentilla reptans L. root via Nrf2 pathway in an isolated rat heart ischemia/reperfusion model.

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

Department of Pharmacognosy, Faculty of Pharmacy, Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Life Sci. 2018 Dec 15;215:216-226. doi: 10.1016/j.lfs.2018.11.021. Epub 2018 Nov 10.

Abstract

BACKGROUND

Previous studies have shown that proanthocyanidins have cardioprotective effects which are mediated via the release of nitric oxide (NO) ultimately resulting in increasing the antioxidant activity. We have investigated to show whether 1) the total extract and ethyl acetate fraction (Et) of Potentilla reptans root have an ischemic preconditioning (IPC) effect, 2) P. reptans has antioxidant and cardioprotective effects mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and scavenging of reactive oxygen species (ROS), 3) NO, caspase-3 and Bcl-2/Bax are involved in the IPC effect of P. reptans.

METHODS

Male Wistar rats were divided into 10 groups. The isolated hearts were subjected to 30 min of ischemia and 100 min of reperfusion. The P. reptans was applied before the main ischemia. The infarct size was estimated by triphenyl-tetrazolium chloride staining. The hemodynamic parameters and ventricular arrhythmias were calculated during the reperfusion. Antioxidant markers and immunohistochemistry assays were determined at the end of the protocol.

RESULTS

The Et significantly decreased the infarct size, arrhythmia scores, ventricular fibrillation incidence, and enhanced the hemodynamic parameters in a concentration-dependent manner against the ischemia/reperfusion group. SOD and CAT activity were increased and MDA level was decreased in response to the Et. Meanwhile, Et attenuated the suppression of Nrf2 expression and reduced the apoptotic indexes. The cardioprotective effect of P. reptans was abrogated by L-NAME.

CONCLUSIONS

P. reptans demonstrated that the cardioprotective preconditioning effects via NO release, Nrf2 pathway, and antioxidant activity lead to a decrease in the apoptotic index.

摘要

背景

先前的研究表明,原花青素具有心脏保护作用,其作用机制是通过释放一氧化氮(NO),最终增加抗氧化活性。我们研究了 1)獐牙菜根的总提取物和乙酸乙酯部分(Et)是否具有缺血预处理(IPC)作用,2)獐牙菜是否具有通过核因子红细胞 2 相关因子 2(Nrf2)途径和清除活性氧(ROS)介导的抗氧化和心脏保护作用,3)NO、半胱天冬酶-3 和 Bcl-2/Bax 是否参与獐牙菜的 IPC 作用。

方法

雄性 Wistar 大鼠分为 10 组。分离的心脏经历 30 分钟的缺血和 100 分钟的再灌注。獐牙菜在主要缺血前应用。用三苯基四唑氯化物染色法估计梗死面积。在再灌注期间计算血流动力学参数和心室性心律失常。在方案结束时测定抗氧化标记物和免疫组织化学测定。

结果

Et 显著降低了缺血/再灌注组的梗死面积、心律失常评分、心室颤动发生率,并以浓度依赖的方式增强了血流动力学参数。SOD 和 CAT 活性增加,MDA 水平降低。同时,Et 减弱了 Nrf2 表达的抑制作用,并降低了凋亡指数。獐牙菜的心脏保护作用被 L-NAME 阻断。

结论

獐牙菜表明,通过释放 NO、Nrf2 途径和抗氧化活性发挥心脏保护预处理作用,导致凋亡指数降低。

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